Computational analysis of resistance mutations in the hepatitis C virus

Análisis computacional de resistencia a mutaciones en el virus de la hepatitis C

  • Karina Salvatierra
  • Hector Florez Universidad Distrital Francisco José de Caldas
Palabras clave: antivirals, computational analysis, hepatitis C virus, NS5B (en_US)
Palabras clave: antivirales, análisis computacional, virus de la hepatitis C, NS5B (es_ES)

Resumen (en_US)

Hepatitis C virus (HCV) continues to be a public health problem worldwide. The development of drugs that target virus proteins such as NS5B, aims to provide more effective treatment in the future. These direct-acting antivirals (DAAs) have demonstrated potent in vitro and in vivo effect; however, mutations have been described in HCV NS5B associated with resistance to DAA. Detecting mutations that are resistant to DAAs is important to prevent potential treatment failures. In this work, we developed a software to analyze mutations that are resistant to DAAs in NS5B gene of HCV. For this, we used the NS5B gene sequence isolate Con1 genotype 1b HCV, based on the main positions mutations associated with resistance to DAAs in vitro and in vivo described in the literature. The software algorithm allows computer analysis of possible changes in nucleotide and amino acid positions associated with resistance mutations to DAAs in NS5B of HCV

Resumen (es_ES)

El virus de la hepatitis C (VHC) continúa siendo un problema de salud pública en todo el mundo. El desarrollo de medicamentos que se dirigen a las proteínas del virus como NS5B, tiene como objetivo proporcionar un tratamiento más eficaz en el futuro. Estos antivirales de acción directa (DAA) han demostrado un potente efecto in vitro e in vivo; sin embargo, se han descrito mutaciones en la NS5B del VHC asociada a la resistencia a DAA. La detección de mutaciones que son resistentes a DAA es importante para evitar posibles fallas de tratamiento. En este trabajo, desarrollamos un software para analizar mutaciones que son resistentes a los DAA en el gen NS5B del VHC. Para esto, utilizamos la secuencia del gen NS5B aislada Con1 genotipo 1b HCV, con base en las principales posiciones asociadas con la resistencia a DAA in vitro e in vivo descritas en la literatura. El algoritmo del software permite el análisis computacional de posibles cambios en las posiciones de nucleótidos y aminoácidos asociadas con mutaciones de resistencia a DAA en NS5B de HCV.

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Biografía del autor/a

Hector Florez, Universidad Distrital Francisco José de Caldas

Ingeniero Electrónico, Ingeniero de sistemas, Magister en Ciencias de la Información y las Comunicaciones, especialista en Alta Gerencia, Magister en Gestion de Organizaciones, Doctor (c) en Ingenieria

Docente investigador de la Universidad Distrital Francisco José de Caldas de Bogotá

Referencias

Q. Choo,G. Ku, A. Weiner, L. Overby, D. Bradley, M. Houghton, “Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome”. Science, New Series, vol. 244, n°. 4902, pp. 359-362, 1989. https://doi.org/10.1126/science.2523562

World Health Organization (OMS) “Guidelines for the screening, care and treatment of persons with hepatitis C infection”, julio de 2017, [Online] Available: http://apps.who.int/iris/bitstream/handle/10665/111747/9789241548755_eng.pdf;jsessionid=989D7EA7EE4A59CFD8179A760BD71236?sequence=1

C. Sarrazin, T. Berg, R.S. Ross, P. Schirmacher, H. Wedemeyer, U. Neumann, et al., “Prophylaxis, diagnosis and therapy of hepatitis C virus (HCV) infection: the German guidelines on the management of HCV infection”. Z Gastroenterol, vol. 48, n°. 2, pp. 289-351, 2010. https://doi.org/10.1055/s-0028-1110008

M.P. Manns, H. Wedemeyer, M. Cornberg, “Treating viral hepatitis C: efficacy, side effects, and complications”. Gut., vol. 55, n°. 9, pp. 1350-9, 2006. https://doi.org/10.1136/gut.2005.076646

V. Soriano, E. Vispo, E. Poveda, P. Labarga, L. Martin-Carbonero, J. V. Fernandez-Montero, et al., “Directly acting antivirals against hepatitis C virus”. J AntimicrobChemother, vol. 66, n°. 8, pp. 1673-86, 2011. https://doi.org/10.1093/jac/dkr215

A. J. Thompson, S. Locarnini, “Direct-acting antiviral agents for the treatment of HCV”. AntivirTher., vol. 17, n°. 6 Pt B, pp. 1105-7, 2012.

A. D. Kwong, L. McNair, I. Jacobson, S. George, “Recent progress in the development of selected hepatitis C virus NS3/4A protease and NS5B polymerase inhibitors”. CurrOpinPharmacol., vol. 8, n°. 5, pp. 522-31, 2008. https://doi.org/10.1016/j.coph.2008.09.007

C. Welsch, F. S. Domingues, S. Susser, I. Antes, C. Hartmann, G. Mayr, et al., “Molecular basis of telaprevir resistance due to V36 and T54 mutations in the NS3/4A protease of the hepatitis C virus”. Genome Biol., vol.9, n°. 1, pp. R16, 2008. https://doi.org/10.1186/gb-2008-9-1-r16

D. L. Wyles, “Antiviral resistance and the future landscape of hepatitis C virus infection therapy”. J Infect Dis., vol. 207, Suppl 1, pp. S33-9, 2013. https://doi.org/10.1093/infdis/jis761

D. L. Wyles, J. A. Gutierrez, “Importance of HCV genotype 1 subtypes for drug resistance and response to therapy”. J Viral Hepat., vol. 21, n°. 4, pp. 229-40, 2014. https://doi.org/10.1111/jvh.12230

I. Najera, “Resistance to HCV nucleoside analogue inhibitors of hepatitis C virus RNA-dependent RNA polymerase”. CurrOpinVirol., vol. 3, n°. 5, pp. 508-13, 2013. https://doi.org/10.1016/j.coviro.2013.08.011

K. J. Cortez, F. Maldarelli, “Clinical management of HIV drug resistance”. Viruses, vol. 3, n°. 4, pp. 347-78, 2011. https://doi.org/10.3390/v3040347

P. Halfon, C. Sarrazin, “Future treatment of chronic hepatitis C with direct acting antivirals: is resistance important?”. Liver Int., vol. 32, Suppl 1, pp. 79-87, 2012. https://doi.org/10.1111/j.1478-3231.2011.02716.x

K. Salvatierra, S. Fareleski, A. Forcada, F. X. López-Labrador, “Hepatitis C virus resistance to new specifically-targeted antiviral therapy: A public health perspective”. World J Virol., vol. 2, n°. 1, pp. 6-15, 2013. https://doi.org/10.5501/wjv.v2.i1.6

X. Tong, S. Le Pogam, L. Li , K. Haines, K. Piso, V. Baronas, et al., “In vivo emergence of a novel mutant L159F/L320F in the NS5B polymerase confers low-level resistance to the HCV polymerase inhibitors mericitabine and sofosbuvir”. J Infect Dis., vol. 209, n°. 5, pp. 668-75, 2014. https://doi.org/10.1093/infdis/jit562

X. Tong, L. Li, K. Haines, I. Najera, “The NS5B S282T Resistant Variant and Two Novel Amino Acid Substitutions That Affect Replication Capacity Were Identified in Hepatitis C Virus Infected Patients Treated with Mericitabine and Danoprevir”. Antimicrob Agents Chemother, vol. 58, n°. 6, pp. 3105-3114, 2014. https://doi.org/10.1128/AAC.02672-13

J. M. Pawlotsky, “New antiviral agents for hepatitis C”. F1000 Biol Rep., vol. 4, n°. 5, pp. 1-7, 2012. https://doi.org/10.3410/B4-5

M. J. Sofia, W. Chang, P. A. Furman, R. T. Mosley, B. S. Ross, “Nucleoside, nucleotide, and non-nucleoside inhibitors of hepatitis C virus NS5B RNA-dependent RNA-polymerase”. J Med Chem., vol. 55, n°. 6, pp. 2481-531, 2012. https://doi.org/10.1021/jm201384j

A. J. Thompson, J. G.McHutchison, “Antiviral resistance and specifically targeted therapy for HCV (STAT-C)”. J ViralHepat., vol. 16, n°. 6, pp. 377-87, 2009. https://doi.org/10.1111/j.1365-2893.2009.01124.x

Cómo citar
[1]
K. Salvatierra y H. Florez, Análisis computacional de resistencia a mutaciones en el virus de la hepatitis C, rvin, vol. 15, n.º 1, pp. 27-33, may 2018.
Publicado: 2018-05-17
Sección
Investigación y Desarrollo